Pendulum of data swings back and forth on flu vaccines
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LAIV, IIV almost equally effective against influenza

When vaccinating children against influenza, inactivated and live attenuated influenza vaccines show little significant difference in effectiveness against nearly all strains of the virus, according to a new study in Pediatrics.

However, the study – which examined the effectiveness of IIV and LAIV across four consecutive influenza seasons between 2010 and 2014 – cautions that the 2013-2014 season’s A/(H1N1)pdm09 showed an uncharacteristically large gap in effectiveness favoring IIV, a discrepancy likely due to a problem with a vaccine component in LAIV. (Pediatrics. 2016;137(2):e20153279)

“We found that lower LAIV effectiveness in 2013-2014 was specific to the A/(H1N1)pdm09 vaccine component and was consistent with a previously unexamined effect during the 2010-2011 influenza season,” Jessie R. Chung of the influenza division at the Centers for Disease Control and Prevention and associates wrote, adding that the impetus for the study was the lack of available data “from observational studies after the 2009 pandemic on relative effectiveness of LAIV and IIV in children and adolescents.”

Ms. Chung* and coinvestigators enrolled children aged 2-17 years from clinics and hospitals in Michigan, New York, Pennsylvania, Tennessee, Texas, Washington, and Wisconsin during the 2010-2011, 2011-2012, 2012-2013, and 2013-2014 influenza seasons. Children brought in with symptoms of acute respiratory illness – cough, fever, or feverishness – had nasal and throat swabs collected to test for presence and type of influenza.

In total, 7,718 subjects were evaluated across the four influenza seasons, but after excluding subjects for various reasons – unknown vaccine type, indeterminate vaccine status, and inconclusive reverse transcription polymerase chain reaction results, among others – 6,819 subjects were included for vaccine effectiveness analysis, of which 2,703 were ultimately matched age appropriately and placed into IIV and LAIV cohorts for comparison. The IIV cohort consisted of 2,066 individuals (76.4%), while the LAIV cohort had 637 (23.6%).

During the 2010-2011 season, 66 of the 477 IIV subjects contracted influenza, versus 21 of 116 who received LAIV (14% vs. 18%, respectively). In the 2011-2012 season, 51 of the 499 IIV subjects (10%) contracted influenza, compared with 12 of the 152 LAIV subjects (8%). In the 2012-2013 season, 198 of the 622 IIV subjects (32%) contracted influenza, versus 61 of the 205 LAIV subjects (30%). But, in the 2013-2014 season, 36 of the 468 IIV subjects (8%) contracted influenza, versus 34 of the 164 LAIV subjects (21%).

After adjustment for age and season, the odds ratio for the 2013-2014 season was significantly higher than those of the other seasons across the entire age spectrum of 2-17 years: 2.88, compared with 1.49 (2010-2011), 0.67 (2011-2012), and 0.92 (2012-2013).

When comparing influenza type/subtype, adjusted odds ratio was 5.53 for those with A/(H1N1)pdm09 in the 2010-2011 season, compared with 2.65 for those with the same in the 2013-2014 season. Those with A/H3N2 did not show as significant a difference across seasons (2010-2013), nor did those with influenza type B (2010-2011, 2012-2013).

“We found no statistically significant difference in LAIV effectiveness compared with IIV against medically attended, laboratory-confirmed influenza illness due to A/H3N2 or B viruses,” Ms. Chung and colleagues concluded. “We found significantly higher odds of influenza A/(H1N1)pdm09 among participants vaccinated with LAIV, compared with IIV, [but] reasons for lower effectiveness of LAIV against the A/(H1N1)pdm09 virus, compared with IIV are not fully understood.”

The investigators added that “the finding appears to be specific to the A/(H1N1)pdm09 vaccine component; we did not detect any statistically significant differences in effectiveness for the other components.” Three previous randomized controlled trials indicated that trivalent LAIV was just as effective, if not more so, than IIV, making the findings of this study surprising and “unexpected,” the authors noted.

This study was supported by the CDC through cooperative agreements with a variety of universities and foundations, and funded by the National Institutes of Health. Ms. Chung and associates reported no relevant financial disclosures.

*A previous version of this story misstated Jessie Chung’s academic title. Ms. Chung holds a Master’s in public health.

[email protected]

References

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Influenza vaccination has been recommended for everyone for the past few years. Acceptance of this recommendation has been variable, and vaccine failures do not help the cause of convincing our patients to accept vaccination. In the paper by Chung et al. from the CDC and other coinvestigators who are prominent in influenza research, we learn that the live attenuated intranasally administered flu vaccine was significantly inferior to the killed injection administered flu vaccine for one of the type A flu strains. As a consequence, more kids vaccinated with the live attenuated vaccine got the flu. So parents who claim “the flu shot does not work” were partially correct more often since the 2009 flu season, if their child got the intranasal flu vaccine. However, neither the intranasal nor the injectable flu vaccine have an exceptionally high efficacy because the calculations by the authors for the study described and by citation of prior studies we are reminded that vaccine efficacy varies by strain and yearly by the season between 45% and 71%. We need to have better flu vaccines.

Dr. Michael E. Pichichero

At Legacy Pediatrics, where I am in part-time private practice, we have seen increasing requests for the intranasal flu vaccine each year because parents and kids who can voice their wishes don’t want the shot. Our nurses like it, too, because the crying, wailing, and fighting to hold the kid down is avoided. There had been some reports before 2009 that the intranasal flu vaccine was more effective than the shot. But those of us who have been around long enough practicing medicine have learned about the pendulum of data and opinion sometimes swings back and forth. The article by Chung et al. reminds us once again of this reality.

Dr. Michael E. Pichichero is at the University of Rochester (N.Y.) Medical Center. He has received investigator-initiated grants from Sanofi Pasteur to study novel pneumococcal protein vaccines over the past 3 years and currently but has received no funding from Sanofi regarding injectable influenza vaccine. He also has conducted research with study coauthor Dr. John J. Treanor that was supported by MedImmune, who makes the intranasal flu vaccine.

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Body

Influenza vaccination has been recommended for everyone for the past few years. Acceptance of this recommendation has been variable, and vaccine failures do not help the cause of convincing our patients to accept vaccination. In the paper by Chung et al. from the CDC and other coinvestigators who are prominent in influenza research, we learn that the live attenuated intranasally administered flu vaccine was significantly inferior to the killed injection administered flu vaccine for one of the type A flu strains. As a consequence, more kids vaccinated with the live attenuated vaccine got the flu. So parents who claim “the flu shot does not work” were partially correct more often since the 2009 flu season, if their child got the intranasal flu vaccine. However, neither the intranasal nor the injectable flu vaccine have an exceptionally high efficacy because the calculations by the authors for the study described and by citation of prior studies we are reminded that vaccine efficacy varies by strain and yearly by the season between 45% and 71%. We need to have better flu vaccines.

Dr. Michael E. Pichichero

At Legacy Pediatrics, where I am in part-time private practice, we have seen increasing requests for the intranasal flu vaccine each year because parents and kids who can voice their wishes don’t want the shot. Our nurses like it, too, because the crying, wailing, and fighting to hold the kid down is avoided. There had been some reports before 2009 that the intranasal flu vaccine was more effective than the shot. But those of us who have been around long enough practicing medicine have learned about the pendulum of data and opinion sometimes swings back and forth. The article by Chung et al. reminds us once again of this reality.

Dr. Michael E. Pichichero is at the University of Rochester (N.Y.) Medical Center. He has received investigator-initiated grants from Sanofi Pasteur to study novel pneumococcal protein vaccines over the past 3 years and currently but has received no funding from Sanofi regarding injectable influenza vaccine. He also has conducted research with study coauthor Dr. John J. Treanor that was supported by MedImmune, who makes the intranasal flu vaccine.

Body

Influenza vaccination has been recommended for everyone for the past few years. Acceptance of this recommendation has been variable, and vaccine failures do not help the cause of convincing our patients to accept vaccination. In the paper by Chung et al. from the CDC and other coinvestigators who are prominent in influenza research, we learn that the live attenuated intranasally administered flu vaccine was significantly inferior to the killed injection administered flu vaccine for one of the type A flu strains. As a consequence, more kids vaccinated with the live attenuated vaccine got the flu. So parents who claim “the flu shot does not work” were partially correct more often since the 2009 flu season, if their child got the intranasal flu vaccine. However, neither the intranasal nor the injectable flu vaccine have an exceptionally high efficacy because the calculations by the authors for the study described and by citation of prior studies we are reminded that vaccine efficacy varies by strain and yearly by the season between 45% and 71%. We need to have better flu vaccines.

Dr. Michael E. Pichichero

At Legacy Pediatrics, where I am in part-time private practice, we have seen increasing requests for the intranasal flu vaccine each year because parents and kids who can voice their wishes don’t want the shot. Our nurses like it, too, because the crying, wailing, and fighting to hold the kid down is avoided. There had been some reports before 2009 that the intranasal flu vaccine was more effective than the shot. But those of us who have been around long enough practicing medicine have learned about the pendulum of data and opinion sometimes swings back and forth. The article by Chung et al. reminds us once again of this reality.

Dr. Michael E. Pichichero is at the University of Rochester (N.Y.) Medical Center. He has received investigator-initiated grants from Sanofi Pasteur to study novel pneumococcal protein vaccines over the past 3 years and currently but has received no funding from Sanofi regarding injectable influenza vaccine. He also has conducted research with study coauthor Dr. John J. Treanor that was supported by MedImmune, who makes the intranasal flu vaccine.

Title
Pendulum of data swings back and forth on flu vaccines
Pendulum of data swings back and forth on flu vaccines

When vaccinating children against influenza, inactivated and live attenuated influenza vaccines show little significant difference in effectiveness against nearly all strains of the virus, according to a new study in Pediatrics.

However, the study – which examined the effectiveness of IIV and LAIV across four consecutive influenza seasons between 2010 and 2014 – cautions that the 2013-2014 season’s A/(H1N1)pdm09 showed an uncharacteristically large gap in effectiveness favoring IIV, a discrepancy likely due to a problem with a vaccine component in LAIV. (Pediatrics. 2016;137(2):e20153279)

“We found that lower LAIV effectiveness in 2013-2014 was specific to the A/(H1N1)pdm09 vaccine component and was consistent with a previously unexamined effect during the 2010-2011 influenza season,” Jessie R. Chung of the influenza division at the Centers for Disease Control and Prevention and associates wrote, adding that the impetus for the study was the lack of available data “from observational studies after the 2009 pandemic on relative effectiveness of LAIV and IIV in children and adolescents.”

Ms. Chung* and coinvestigators enrolled children aged 2-17 years from clinics and hospitals in Michigan, New York, Pennsylvania, Tennessee, Texas, Washington, and Wisconsin during the 2010-2011, 2011-2012, 2012-2013, and 2013-2014 influenza seasons. Children brought in with symptoms of acute respiratory illness – cough, fever, or feverishness – had nasal and throat swabs collected to test for presence and type of influenza.

In total, 7,718 subjects were evaluated across the four influenza seasons, but after excluding subjects for various reasons – unknown vaccine type, indeterminate vaccine status, and inconclusive reverse transcription polymerase chain reaction results, among others – 6,819 subjects were included for vaccine effectiveness analysis, of which 2,703 were ultimately matched age appropriately and placed into IIV and LAIV cohorts for comparison. The IIV cohort consisted of 2,066 individuals (76.4%), while the LAIV cohort had 637 (23.6%).

During the 2010-2011 season, 66 of the 477 IIV subjects contracted influenza, versus 21 of 116 who received LAIV (14% vs. 18%, respectively). In the 2011-2012 season, 51 of the 499 IIV subjects (10%) contracted influenza, compared with 12 of the 152 LAIV subjects (8%). In the 2012-2013 season, 198 of the 622 IIV subjects (32%) contracted influenza, versus 61 of the 205 LAIV subjects (30%). But, in the 2013-2014 season, 36 of the 468 IIV subjects (8%) contracted influenza, versus 34 of the 164 LAIV subjects (21%).

After adjustment for age and season, the odds ratio for the 2013-2014 season was significantly higher than those of the other seasons across the entire age spectrum of 2-17 years: 2.88, compared with 1.49 (2010-2011), 0.67 (2011-2012), and 0.92 (2012-2013).

When comparing influenza type/subtype, adjusted odds ratio was 5.53 for those with A/(H1N1)pdm09 in the 2010-2011 season, compared with 2.65 for those with the same in the 2013-2014 season. Those with A/H3N2 did not show as significant a difference across seasons (2010-2013), nor did those with influenza type B (2010-2011, 2012-2013).

“We found no statistically significant difference in LAIV effectiveness compared with IIV against medically attended, laboratory-confirmed influenza illness due to A/H3N2 or B viruses,” Ms. Chung and colleagues concluded. “We found significantly higher odds of influenza A/(H1N1)pdm09 among participants vaccinated with LAIV, compared with IIV, [but] reasons for lower effectiveness of LAIV against the A/(H1N1)pdm09 virus, compared with IIV are not fully understood.”

The investigators added that “the finding appears to be specific to the A/(H1N1)pdm09 vaccine component; we did not detect any statistically significant differences in effectiveness for the other components.” Three previous randomized controlled trials indicated that trivalent LAIV was just as effective, if not more so, than IIV, making the findings of this study surprising and “unexpected,” the authors noted.

This study was supported by the CDC through cooperative agreements with a variety of universities and foundations, and funded by the National Institutes of Health. Ms. Chung and associates reported no relevant financial disclosures.

*A previous version of this story misstated Jessie Chung’s academic title. Ms. Chung holds a Master’s in public health.

[email protected]

When vaccinating children against influenza, inactivated and live attenuated influenza vaccines show little significant difference in effectiveness against nearly all strains of the virus, according to a new study in Pediatrics.

However, the study – which examined the effectiveness of IIV and LAIV across four consecutive influenza seasons between 2010 and 2014 – cautions that the 2013-2014 season’s A/(H1N1)pdm09 showed an uncharacteristically large gap in effectiveness favoring IIV, a discrepancy likely due to a problem with a vaccine component in LAIV. (Pediatrics. 2016;137(2):e20153279)

“We found that lower LAIV effectiveness in 2013-2014 was specific to the A/(H1N1)pdm09 vaccine component and was consistent with a previously unexamined effect during the 2010-2011 influenza season,” Jessie R. Chung of the influenza division at the Centers for Disease Control and Prevention and associates wrote, adding that the impetus for the study was the lack of available data “from observational studies after the 2009 pandemic on relative effectiveness of LAIV and IIV in children and adolescents.”

Ms. Chung* and coinvestigators enrolled children aged 2-17 years from clinics and hospitals in Michigan, New York, Pennsylvania, Tennessee, Texas, Washington, and Wisconsin during the 2010-2011, 2011-2012, 2012-2013, and 2013-2014 influenza seasons. Children brought in with symptoms of acute respiratory illness – cough, fever, or feverishness – had nasal and throat swabs collected to test for presence and type of influenza.

In total, 7,718 subjects were evaluated across the four influenza seasons, but after excluding subjects for various reasons – unknown vaccine type, indeterminate vaccine status, and inconclusive reverse transcription polymerase chain reaction results, among others – 6,819 subjects were included for vaccine effectiveness analysis, of which 2,703 were ultimately matched age appropriately and placed into IIV and LAIV cohorts for comparison. The IIV cohort consisted of 2,066 individuals (76.4%), while the LAIV cohort had 637 (23.6%).

During the 2010-2011 season, 66 of the 477 IIV subjects contracted influenza, versus 21 of 116 who received LAIV (14% vs. 18%, respectively). In the 2011-2012 season, 51 of the 499 IIV subjects (10%) contracted influenza, compared with 12 of the 152 LAIV subjects (8%). In the 2012-2013 season, 198 of the 622 IIV subjects (32%) contracted influenza, versus 61 of the 205 LAIV subjects (30%). But, in the 2013-2014 season, 36 of the 468 IIV subjects (8%) contracted influenza, versus 34 of the 164 LAIV subjects (21%).

After adjustment for age and season, the odds ratio for the 2013-2014 season was significantly higher than those of the other seasons across the entire age spectrum of 2-17 years: 2.88, compared with 1.49 (2010-2011), 0.67 (2011-2012), and 0.92 (2012-2013).

When comparing influenza type/subtype, adjusted odds ratio was 5.53 for those with A/(H1N1)pdm09 in the 2010-2011 season, compared with 2.65 for those with the same in the 2013-2014 season. Those with A/H3N2 did not show as significant a difference across seasons (2010-2013), nor did those with influenza type B (2010-2011, 2012-2013).

“We found no statistically significant difference in LAIV effectiveness compared with IIV against medically attended, laboratory-confirmed influenza illness due to A/H3N2 or B viruses,” Ms. Chung and colleagues concluded. “We found significantly higher odds of influenza A/(H1N1)pdm09 among participants vaccinated with LAIV, compared with IIV, [but] reasons for lower effectiveness of LAIV against the A/(H1N1)pdm09 virus, compared with IIV are not fully understood.”

The investigators added that “the finding appears to be specific to the A/(H1N1)pdm09 vaccine component; we did not detect any statistically significant differences in effectiveness for the other components.” Three previous randomized controlled trials indicated that trivalent LAIV was just as effective, if not more so, than IIV, making the findings of this study surprising and “unexpected,” the authors noted.

This study was supported by the CDC through cooperative agreements with a variety of universities and foundations, and funded by the National Institutes of Health. Ms. Chung and associates reported no relevant financial disclosures.

*A previous version of this story misstated Jessie Chung’s academic title. Ms. Chung holds a Master’s in public health.

[email protected]

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LAIV, IIV almost equally effective against influenza
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LAIV, IIV almost equally effective against influenza
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Key clinical point: Inactivated influenza vaccine was significantly more effective against at least one strain of influenza than live attenuated influenza vaccine in 2013-2014.

Major finding: While no significant differences were seen in influenza rates between the IIV and LAIV cohorts for three consecutive seasons (2010-2013), the A/(H1N1)pdm09 strain of 2013-2014 affected subjects with LAIV at a significantly higher rate than did those with IIV.

Data source: Prospective cohort study of 2,703 children aged 2-17 years vaccinated between 2010 and 2014 with either IIV or LAIV.

Disclosures: This study was supported by the CDC through cooperative agreements with a variety of universities and foundations, and funded by the National Institutes of Health. Dr. Chung and his associates reported no relevant financial disclosures.